Diagnosis and treatment of autoimmune diseases

Abstract

Methods, kits and compositions for diagnosing and treating autoimmune diseases such as rheumatiodi arthritis. Crohn's disease, and ulcerative colitis.

What is claimed is: 
     
       1. A method of analyzing a biological sample, the method comprising:
 (i) providing a biological sample of a human subject suspected of having an autoimmune disease; 
 (ii) measuring a level of cleaved high molecular weight kininogen (HMWK) in the biological sample, 
 (iii) identifying the human subject having a level of cleaved HMWK in the biological sample that is elevated compared to a control sample as having the autoimmune disease, and 
 (iv) administering to the human subject identified in step (iii) a plasma kallikrein (pKal) inhibitor, an anti-inflammatory agent, or a combination thereof; 
 wherein the biological sample and the control sample are a serum sample, a blood sample, or a plasma sample; 
 wherein the autoimmune disease is selected from the group consisting of: inflammatory bowel disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis; and 
 wherein the level of cleaved HMWK is measured by an assay that involves a binding agent specific to cleaved HMWK. 
 
     
     
       2. The method of  claim 1 , wherein the biological sample comprises one or more protease inhibitors, which are added to the biological sample after its collection. 
     
     
       3. The method of  claim 1 , wherein the binding agent is an antibody. 
     
     
       4. The method of  claim 1 , wherein the assay is an enzyme-linked immunosorbent assay (ELISA) or an immunoblotting assay. 
     
     
       5. The method of  claim 1 , wherein the assay is a Western blotting assay. 
     
     
       6. The method of  claim 1 , wherein the autoimmune disease is inflammatory bowel disease. 
     
     
       7. The method of  claim 1 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
       8. The method of  claim 1 , wherein the autoimmune disease is Crohn's disease. 
     
     
       9. The method of  claim 1 , wherein the autoimmune disease is ulcerative colitis. 
     
     
       10. The method of  claim 1 , wherein the pKal inhibitor comprises:
 (i) amino acids 3-60 of SEQ ID NO: 2 or amino acids 1-60 of SEQ ID NO: 2; or 
 (ii) an antibody that binds plasma kallikrein. 
 
     
     
       11. The method of  claim 1 , wherein the anti-inflammatory agent is a steroid or a non-steroidal anti-inflammatory drug (NSAID). 
     
     
       12. The method of  claim 11 , wherein the steroid is cortisol, cortisone, fludrocortisone, prednisone, 6[alpha]-methylprednisone, triamcinolone, betamethasone, or dexamethasone. 
     
     
       13. The method of  claim 11 , wherein the NSAID is aspirin, acetaminophen, tolmetin, ibuprofen, mefenamic acid, piroxicam, nabumetone, rofecoxib, celecoxib, etodolac, or nimesulide.